The basic purpose of this study is to clarify the mechanism of tumor cell destruction by lymphocytes: 1) The research is directed toward determination of the role of the cytolytic lymphocyte mediator lymphotoxin (LT) in vitro by attempting to inhibit tumor cell destruction with anti-lymphotoxin serum. 2) Efforts will be made to detect the presence and levels of LT in human neoplasms by radioimmune assay. 3) Employing isotopically-labeled LT, we will establish the binding affinity to LT-sensitive and -resistant cells to discover if failure of tumor cell destruction may be partly explained by an LT receptor defect in the resistant cells. 4) At the biochemical level, the effect of LT on the cell membrane, the likely target of the mediator, will be examined by studying the synthesis and breakdown of cell membranes of LT-treated cells and the degradation of isolated cell membranes by LT in a cell-free system. We have previously shown that inhibitors of RNA synthesis synergize with LT in destroying target cells in vitro. Therefore we intend to screen inhibitors of RNA synthesis acting at various levels for their capacity to synergize with LT in target cell destruction. Then we would examine these RNA synthesis inhibitors in tumor-bearing animals for their ability to strengthen the relatively weak cellular immune response to neoplasia by synergizing with LT. This might lead to entirely new approaches to the treatment of cancer by accentuating the anti-tumor immune response.